Anika C. Bundscherer

Effects of ketamine, s-ketamine, and MK 801 on proliferation, apoptosis, and necrosis in pancreatic cancer cells

BackgroundAdenocarcinoma of the pancreas is one of the most aggressive cancer diseases affecting the human body. The oncogenic potential of this type of cancer is mainly characterized by its extreme growth rate triggered by the activation of signaling cascades. Modern oncological treatment strategies aim at efficiently modulating specific signaling and transcriptional pathways. Recently, anti-tumoral potential has been proven for several substances that are not primarily used in cancer treatment. In some tumor entities, for example, administration of glutamate antagonists inhibits cell proliferation, cell cycle arrest, and finally cell death.To attain endogenic proof of NMDA receptor type expression in the pancreatic cancer cell lines PaTu8988t and Panc-1 and to investigate the impact of ketamine, s-ketamine, and the NMDA receptor antagonist MK 801 on proliferation, apoptosis, and necrosis in pancreatic carcinoma.MethodsCell proliferation was measured by means of the ELISA BrdU assay, and the apoptosis rate was analyzed by annexin V staining. Immunoblotting were also used.ResultsThe NMDA receptor type R2a was expressed in both pancreatic carcinoma cell lines. Furthermore, ketamine, s-ketamine, and MK 801 significantly inhibited proliferation and apoptosis.ConclusionsIn this study, we showed the expression of the NMDA receptor type R2a in pancreatic cancer cells. The NMDA antagonists ketamine, s-ketamine, and MK 801 inhibited cell proliferation and cell death. Further clinical studies are warranted to identify the impact of these agents on the treatment of cancer patients.

Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons.

Ketamine and its stereoisomer S(+)-ketamine are widely used for sedation in pediatric anesthesia and intensive care medicine. Numerous experimental studies indicate that ketamine is potentially toxic to the developing brain. Here, we examined the long-term effects of NMDA receptor blockade on NMDA receptor subunit expression, alterations in neuronal Ca(2+)-oscillations and apoptosis. Hippocampal neurons, 15 days in culture, were exposed to either S(+)-ketamine or the NMDA receptor blocker MK801 for 24h. Cytosolic Ca(2+)-concentration was determined by fluorescence microscopy and the expression of the NMDA subunits NR1, NR2A and 2B was assessed by qRT-PCR, whereas Western blots and activated Caspase-3 served to measure the extent of apoptosis. Long-term incubation with MK801 or higher doses of S(+)-ketamine resulted in a dose-dependent decreased ability of MK801 to reduce amplitude and frequency of the Ca(2+)-oscillations 15min following washout of the drug. This was accompanied by an increase in NR1 mRNA but not the NR2A and B subunit expression at the same time point. 24h following washout of the specific drug, a significant elevation of the pro-apoptotic marker BAX, as well as activated Caspase-3 positive neurons, could be detected in cultures exposed to 100μM MK801 and 25μM S(+)-ketamine. Here, we show that long-term blockade of the NMDA receptor in developing rat hippocampal neurons significantly increased NR1 subunit expression, and that this was associated with an alteration in neuronal activity. Apoptosis was only induced 24h after withdrawal of long-term blockade for high doses of S(+)-ketamine.

A comparison of fiberoptical guided tracheal intubation via laryngeal mask and laryngeal tube.

Background: Fiberoptical assisted intubation via a placed laryngeal mask airway (LMA) has been described as save and easy procedure to manage a difficult airway. The laryngeal tube (LT) is a promising alternative to the LMA as supraglottic airway device. Fiberoptical assisted intubation via LT is possible, however considered more difficult. The aim of this study was to compare the fiberoptical assisted intubation via LT and LMA. Materials and Methods: A total of 22 anesthesiologists with different levels of experience participated in the study performed on an adult airway model. Primarily the supraglottic device was placed and correct position was confirmed by successful ventilation. A 5 mm internal diameter tracheal tube was loaded onto a flexible 3.6 mm fiberscope and the so prepared device was inserted into the proximal lumen of the LMA or the LT. The glottis was passed under visual control and the tube advanced into the trachea. After removal of the fiberscope, ventilation was examined clinically by inspection. Success rates, procedure time and observed complications of LMA versus LT were compared (U-test; P < 0.05). Results: Placement of the endotracheal tube was successful in all attempts using both the LMA and LT. There was no difference in the time needed for the placement procedure (33 [26-38] s LMA; 35 [32-38] s LT). Only minor technical complications were observed in both groups. Conclusion: A fiberoptical assisted intubation via LT can be considered as a relevant alternative in advanced airway management.

Geriatrics in medical students’ curricula: questionnaire-based analysis

BackgroundDemographic development is accompanied by an increasingly aging society. Concerning medical education, the treatment of older people as well as the scientific research and exploration of ageing aspects in the coming years need to be considered. Aim of the study was to ascertain medical students’ knowledge, interest, and attitudes regarding older patients and geriatric medicine.MethodsEach participant completed a self-designed questionnaire. This questionnaire was based on three validated internationally recognised questionnaires (“Facts on Aging Quiz – FAQ”, “Expectations Regarding Aging – ERA” and the “Aging Semantic Differential – ASD”). The inquiry and survey were performed at the beginning of the summer term in 2012 at the University of Regensburg Medical School.ResultsA total of n = 184/253 (72.7%) students participated in this survey. The results of the FAQ 25+ showed that respondents were able to answer an average of M = 20.4 of 36 questions (56.7%) correctly (Median, Md = 21; SD ±6.1). The personal attitudes and expectations of ageing averaged M = 41.2 points on the Likert-scale that ranged from 0 to 100 (Md = 40.4; SD ±13.7). Respondents’ attitudes towards the elderly (ASD 24) averaged M = 3.5 points on the Likert-scale (range 1–7, Md 3.6, SD ±0.8).ConclusionsIn our investigation, medical students’ knowledge of ageing was comparable to previous surveys. Attitudes and expectations of ageing were more positive compared to previous studies. Overall, medical students expect markedly high cognitive capacities towards older people that can actively prevent cognitive impairment. However, medical students’ personal interest in medicine of ageing and older people seems to be rather slight.